Methods and compositions for the prevention and treatment of kidney disease

ABSTRACT

Compositions for preventing or treating kidney disease comprising one or more food ingredients containing relatively low amounts of protein, sodium, and potassium, typically protein in amounts of from about 5% to about 40%, sodium in amounts of from about 0.01% to about 1%, and potassium in amounts of from about 0.01% to about 1%, and methods comprising administering such compositions to patients susceptible to or suffering from kidney disease for the purpose of preventing or treating kidney disease.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Ser.No. 60/695,152 filed Jun. 29, 2005, the disclosure of which isincorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to compositions and methods forcombating kidney disease and particularly to the use of foodcompositions for preventing or treating kidney disease.

2. Description of the Prior Art

Chronic kidney disease currently affects as many as 20 millionAmericans. Unfortunately, the incidence and prevalence of the diseasehave doubled in the past few years. The increase is most likelyattributable to improved treatments for hypertension, diabetes, andcoronary disease. These improvements have increased the longevity foraffected patients and, therefore, their likelihood of developing chronickidney disease. Estimated medical and other economic costs of chronickidney disease are expected to approach $28 billion annually within afew years.

The effect of dietary protein restriction on kidney disease is thesubject of debate. Some studies suggest that dietary protein restrictionslows the progression of kidney disease, particularly in patients withdiabetes (Pedrini M T, Levey A S, Lau J, Chalmers T C, Wang P H. Theeffect of dietary protein restriction on the progression of diabetic andnondiabetic renal diseases: a meta-analysis. Ann Intern Med 1996;124:627-32). However, these studies were inconclusive by the use ofACE-inhibitor therapy on the rate of disease progression. One studyattempted to determine a level of protein intake that might reduce therisk of kidney disease progression and also minimize the risk ofmalnutrition (Klahr S, Levey A S, Beck G J, Caggiula A W, Hunsicker L,Kusek J W, et al. The effects of dietary protein restriction andblood-pressure control on the progression of chronic renal disease.Modification of Diet in Renal Disease Study Group. N Engl J Med 1994;330:877-84). The study evaluated three levels of dietary protein intakeand found that a very-low-protein diet slightly decreased the rate ofprogression of proteinuria compared with diets with higher proteinintake. The very-low-protein diet did not result in malnutrition but italso did not decrease the progression of kidney disease.

Further, diets that contain very low amounts of protein and othernutrients may be beneficial for preventing or treating kidney diseasebut can cause undesirable weight loss and muscle wasting. In contrast,diets that have higher amounts of protein and other nutrients aregenerally not useful for preventing or treating kidney disease.Similarly, there is no useful information on the combination ofnutrients that can be used to prevent or treat kidney disease. There is,therefore, a need for food compositions having defined ranges of proteinand other nutrients that are beneficial for preventing or treatingkidney disease while avoiding the undesirable weight loss and musclewasting.

SUMMARY OF THE INVENTION

It is, therefore, an object of the present invention to providecompositions and methods for preventing or treating kidney disease.

It is another object of the invention to provide articles of manufacturein the form of kits that contain combinations of compositions anddevices useful for preventing or treating kidney disease.

It is a further object of the invention to provide a means forcommunicating information about or instructions for using a foodcomposition comprising one or more food ingredients containingrelatively low amounts of protein, sodium, and potassium for preventingor treating kidney disease.

These and other objects are achieved using novel compositions andmethods for preventing or treating kidney disease. The compositionscomprise one or more food ingredients containing relatively low amountsof protein, sodium, and potassium, typically protein in amounts of fromabout 5% to about 40%, sodium in amounts of from about 0.01% to about1%, and potassium in amounts of from about 0.01% to about 1%. Themethods comprise administering such compositions to patients susceptibleto or suffering from kidney disease. Kits comprising a food compositionin combination with renal drugs, renal diagnostic devices, and means forcommunicating information about and instructions for using the inventionare also provided.

Other and further objects, features, and advantages of the presentinvention will be readily apparent to those skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION Definitions

The term “patient” means a human or other animal susceptible to orsuffering from kidney disease, including avian, bovine, canine, equine,feline, hicrine, murine, ovine, and porcine animals. Preferably, thepatient is a canine or feline.

The term “relatively low amounts” means amounts of protein, sodium, andpotassium that prevent or treat kidney disease but not amounts that areso low that they cause undesirable weight loss and muscle wasting.

The term “extremely low amounts” means amounts of protein, sodium,potassium that may prevent or treat kidney disease but amounts that areso low that they cause undesirable weight loss and muscle wasting.

The term “renal drug” means any compound, composition, or drug usefulfor preventing or treating kidney disease.

The term “single package” means that the components of a kit arephysically associated in or with one or more containers and considered aunit for manufacture, distribution, sale, or use. Containers include,but are not limited to, bags, boxes, bottles, shrink wrap packages,stapled or otherwise affixed components, or combinations thereof.

The term “virtual package” means that the components of a kit areassociated by directions on one or more physical or virtual kitcomponents instructing the user how to obtain the other components,e.g., in a bag containing one component and directions instructing theuser to go to a website, contact a recorded message, view a visualmessage, or contact a caregiver or instructor to obtain instructions onhow to use the kit.

The term “in conjunction” means that one or more of the compositions andcompounds (e.g., renal drugs or composition components) of the presentinvention are administered to a patient (1) together in a foodcomposition or (2) separately at the same or different frequency usingthe same or different administration routes at about the same time orperiodically. “Periodically” means that the compositions, foodcompositions, and compounds are administered on a dosage scheduleacceptable for a specific composition, food composition, and compoundand that the food compositions are administered or fed to a patientroutinely as appropriate for the particular patient. “About the sametime” generally means that the compositions, composition components,renal drugs, and food compositions are administered at the same time orwithin about 72 hours of each other. In conjunction specificallyincludes administration schemes wherein renal drugs are administered fora prescribed period and the compositions are administered indefinitely.

This invention is not limited to the particular methodology, protocols,and reagents described herein because they may vary. Further, theterminology used herein is for the purpose of describing particularembodiments only and is not intended to limit the scope of the presentinvention. As used herein and in the appended claims, the singular forms“a,” “an,” and “the” include plural reference unless the context clearlydictates otherwise, e.g., reference to “a method” or “a foodcomposition” includes a plurality of such methods or compositions.Similarly, the words “comprise”, “comprises”, and “comprising” are to beinterpreted inclusively rather than exclusively.

Unless defined otherwise, all technical and scientific terms and anyacronyms used herein have the same meanings as commonly understood byone of ordinary skill in the art in the field of the invention. Althoughany methods and materials similar or equivalent to those describedherein can be used in the practice of the present invention, thepreferred methods, devices, and materials are described herein.

All patents, patent applications, and publications mentioned herein areincorporated herein by reference to the extent allowed by law for thepurpose of describing and disclosing the compounds, processes,techniques, procedures, technology, articles, and other compositions andmethods disclosed therein that might be used with the present invention.However, nothing herein is to be construed as an admission that theinvention is not entitled to antedate such disclosure by virtue of priorinvention.

The Invention

In one aspect, the present invention provides a food composition forpreventing or treating kidney disease. The food composition comprisesone or more food ingredients containing relatively low amounts ofprotein, sodium, and potassium. The invention is based upon the noveldiscovery that kidney function can be altered by administering thecomposition to a patient and that altering kidney function with thecomposition can prevent or treat kidney disease. The compositioncontains a novel combination of ingredients in specific amounts thathave been found to be useful to prevent and/or treat kidney disease.

In one embodiment, the food composition comprises one or more foodingredients containing protein in amounts of from about 5% to about 40%,sodium in amounts of from about 0.01% to about 1%, and potassium inamounts of from about 0.01% to about 1%. In another embodiment, the foodcomposition comprises one or more food ingredients containing protein inamounts of from about 8% to about 25%, sodium in amounts of from about0.05% to about 0.6%, and potassium in amounts of from about 0.05% toabout 0.6%. in a further embodiment, the food composition comprises oneor more food ingredients containing protein in amounts of from about 10%to about 16%, sodium in amounts of from about 0.1% to about 0.5%, andpotassium in amounts of from about 0.1% to about 0.5%.

All percentages expressed herein are on a weight by dry matter basisunless specifically stated otherwise. In a further, embodiment, the foodcomposition comprises one or more food ingredients containing protein inamounts of from about 5% to about 30%, sodium in amounts of from about0.01% to about 2%, potassium in amounts of from about 0.01% to about 2%,and phosphorous in amounts of from about 0.2% to about 1%.

The food ingredients useful in the present invention include any foodingredient suitable for consumption by a patient. Typical foodingredients include but are not limited to fats, carbohydrates,proteins, fibers, and nutrients such as vitamins, minerals, and traceelements. Skilled artisans can select the amount and type of foodingredients for a typical food based upon the dietary requirements ofthe patient, e.g., the patient's species, age, size, weight, health, andfunction.

The food composition can comprise 100% of any particular food ingredientof can comprise a mixture of food ingredients in various proportions. inpreferred embodiments, the food composition comprises a combination offood ingredients in amounts of from about 5% to about 40% protein, fromabout 0.01% to about 1% sodium, from about 0.01% to about 1% potassium,from about 0% to about 50% fat, from about 0% to about 75% carbohydrate,from about 0% to about 40% dietary fiber, and from about 0% to about 15%of one or more nutrients.

The fat and carbohydrate food ingredient is obtained from a variety ofsources such as animal fat, fish oil, vegetable oil, meat, meatby-products, grains, other animal or plant sources, and mixturesthereof. Grains include wheat, corn, barley, and rice.

The protein food ingredient is obtained from a variety sources such asplants, animals, or both. Animal protein includes meat, meatby-products, dairy, and eggs. Meats include the flesh from poultry,fish, and animals such as cattle, swine, sheep, goats, and the like.Meat by-products include lungs, kidneys, brain, livers, stomachs, andintestines. The protein food ingredient may also be free amino acidsand/or peptides. Preferably, the protein food ingredient comprises meat,a meat by-product, dairy products, or eggs.

The fiber food ingredient is obtained from a variety of sources such asvegetable fiber sources, e.g., cellulose, beet pulp, peanut hulls, andsoy fiber.

The nutrients are obtained from a variety of sources known to skilledartisans, e.g., vitamin and mineral supplements and food ingredients.Vitamins and minerals can be included in amounts required to avoiddeficiency and maintain health. These amounts are readily available inthe art. The National Research Council (NRC) provides recommendedamounts of such nutrients for farm animals. See, e.g., NutrientRequirements of Swine (10th Rev. Ed., Nat'l Academy Press, Wash. D.C.,1998), Nutrient Requirements of Poultry (9th Rev. Ed., Nat'l AcademyPress, Wash. D.C., 1994), Nutrient Requirements of Horses (5th Rev. Ed.,Nat'l Academy Press, Wash. D.C., 1989). The American Feed ControlOfficials (AAFCO) provides recommended amounts of such nutrients fordogs and cats. See American Feed Control Officials, Inc., Officialpublication, pp. 129-137 (2004). Vitamins generally useful as foodadditives include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitaminB12, vitamin D, biotin, vitamin K, folic acid, inositol, niacin, andpantothenic acid. Minerals and trace elements useful as food additivesinclude calcium, phosphorus, sodium, potassium, magnesium, copper, zinc,chloride, iron, selenium, iodine, and iron.

The food compositions may contain additions ingredients such asvitamins, minerals, fillers, palatability enhancers, binding agents,flavors, stabilizers, emulsifiers, sweeteners, colorants, buffers,salts, coatings, and the like known to skilled artisans. Stabilizersinclude substances that tend to increase the shelf life of thecomposition such as preservatives, synergists and sequestrants,packaging gases, stabilizers, emulsifiers, thickeners, gelling agents,and humectants. Examples of emulsifiers and/or thickening agents includegelatin, cellulose ethers, starch, starch esters, starch ethers, andmodified starches. Specific amounts for each composition component, foodingredient, and other ingredients will depend on a variety of factorssuch as the particular components and ingredients included in thecomposition; the species of patient; the patient's age, body weight,general health, sex, and diet; the patient's consumption rate; the typeof kidney disease being treated; and the like. Therefore, the componentand ingredient amounts may vary widely and may deviate from thepreferred proportions described herein.

The food compositions may be prepared in a canned or wet form usingconventional food preparation processes known to skilled artisans.Typically, ground animal proteinaceous tissues are mixed with the otheringredients such as fish oils, cereal grains, balancing ingredients,special purpose additives (e.g., vitamin and mineral mixtures, inorganicsalts, cellulose and beet pulp, bulking agents, and the like) and waterin amounts sufficient for processing. These ingredients are mixed in avessel suitable for heating while blending the components. Heating ofthe mixture is effected using any suitable manner, e.g., direct steaminjection or using a vessel fitted with a heat exchanger. Following theaddition of the last ingredient, the mixture is heated to a temperatureof from about 50° F. to about 212° F. Temperatures outside this rangeare acceptable but may be commercially impractical without use of otherprocessing aids. When heated to the appropriate temperature, thematerial will typically be in the form of a thick liquid. The thickliquid is filled into cans. A lid is applied, and the container ishermetically sealed. The sealed can is then placed into conventionalequipment designed to sterilize the contents. Sterilization is usuallyaccomplished by heating to temperatures of greater than about 230° F.for an appropriate time depending on the temperature used, thecomposition, and similar factors. The compositions of the presentinvention can be added to the food compositions before, during, or afterpreparation.

The food compositions may be prepared in a dry form using conventionalprocesses known to skilled artisans. Typically, dry ingredients such asanimal protein, plant protein, grains, and the like are ground and mixedtogether. Moist or liquid ingredients, including fats, oils, animalprotein, water, and the like are then added to and mixed with the drymix. The mixture is then processed into dry food pieces.

The food compositions can be in any form useful for feeding thecomposition to a patient, e.g., kibbles, treats, and toys for animalfood. Kibbles are generally formed using an extrusion process in whichthe mixture of dry and wet ingredients is subjected to mechanical workat a high pressure and temperature and forced through small openings andcut off into kibble by a rotating knife. The wet kibble is then driedand optionally coated with one or more topical coatings such as flavors,fats, oils, powders, and the like. Kibble also can be made from thedough using a baking process, rather than extrusion, wherein the doughis placed into a mold before dry-heat processing. Treats includecompositions that are given to an animal to entice the animal to eatduring a non-meal time, e.g., dog bones or biscuits for canines. Treatsmay be nutritional wherein the composition comprises one or morenutrients or and may have a food-like composition. Non-nutritionaltreats encompass any other treats that are non-toxic. The composition orcomponents are coated onto the treat, incorporated into the treat, orboth. Treats of the present invention can be prepared by an extrusion orbaking process similar to those used for dry food. Other processes alsomay be used to either coat the composition on the exterior of existingtreat forms or inject the composition into an existing treat form. Toysinclude chewable toys such as artificial bones and food compositionsshaped to resemble natural foods that are appealing to the animal. Thefood composition of the present invention can comprise the toy or canform a coating on the surface of the toy or on the surface of acomponent of the toy. The composition can be incorporated partially orfully throughout the toy or both. In one embodiment, the composition isorally accessible by the intended user. There are a wide range ofsuitable toys known to skilled artisans, e.g., as shown in U.S. Pat.Nos. 5,339,771 and 5,419,283. The present invention encompassespartially consumable toys, e.g., toys comprising plastic components, andfully consumable toys, e.g., various artificial bones and similar foods.Further, the invention encompasses toys for both human and non-humanuse, particularly toys for companion, farm, and zoo animal use, and moreparticularly for feline and canine use.

In another aspect, the present invention provides the food compositionsof the present invention further comprising one or more renal drugs.Renal drugs useful in the invention are any renal drugs known to skilledartisans to be useful for combating kidney disease. Preferred drugsinclude lysosome-activating compounds such as those described in U.S.Pat. No. 6,589,748, triterpene saponins such as those described in U.S.Pat. No. 6,784,159, activin inhibitors such as those described in U.S.Pat. No. 6,599,876 and US Patent Application Number (USPAN) 20020028762,integrin receptor inhibitors and TGF inhibitors such as those describedin U.S. Pat. No. 6,492,325, TGF activation inhibitors such as thosedescribed in U.S. Pat. No. 6,458,767, and insulin-like growth factor(IGF) as described in U.S. Pat. No. 5,723,441. Most Preferred drugsinclude Converting Enzyme (ACE) inhibitors, androgens, erythropoiten,and calcitriol. Angiotensin and endothelin are potent systemicvasoconstrictors with specific intrarenal effects that contribute toprogressive renal injury. A variety of renal drugs are used to mitigatethe effect of these vasoconstrictors. Angiotensin converting enzymeinhibitors (enalapril—Enacard and Vasotec and benazepril—Lotensin) havebeen associated with a reduction in the severity of proteinuria andslowing of progression of renal failure. The ACE inhibitor enalapril(Enacard, Vasotec) limits glomerular and systemic hypertension,proteinuria, and glomerular and tubulointerstitial lesions. Angiotensinblockers and endothelin inhibitors have beneficial effects in renaldisease. Vasopeptide inhibitors are agents that inhibit both ACE andneutral endopeptidase, an enzyme involved in the breakdown ofnatriuretic peptides, adrenomedullin, and bradykinin. These renal drugsdecrease angiotenin II production and increase accumulation ofvasodilators. Renal patients with systemic hypertension respond tocalcium channel blockers such as amlodipine (Norvasc). Uremic gastritis(esophagitis, gastritis, gastric ulceration and hemorrhage) is treatedwith H2 receptor antagonists (cimetidine—Tagamet, famotidine—Pepcid),proton pump blockers (omeprazole—Prilosec), cytoprotective agents(misoprostol—Cytotec), and antiemetic drugs that effect the emeticcenter (chlorpromazine—Thorazine, perchlorperazine—Compazine,metoclopramide—Reglan). Androgens or anabolic steroids (Stanozol,Winstrol-V) are used in the treatment of anemia associated with chronicrenal failure. Hormone replacement therapy using recombinant human (orother species) erythropoiten (Epoetin alpha, Epogen, Procrit) is thetreatment of choice for severe anemia associated with renal failure.Phosphate binders (aluminum hydroxide—Amphojel, aluminumcarbonate—Basaljel) are used to control hyperphosphatemia and secondaryrenal hyperparathyroidism. Calcitriol (1, 25-dihydroxycholecalciferol)(Rocaltrol) and vitamin 1) analogues cause a calcium-independentsuppression of parathyroid hormone (PTH). Administration of phosphatebinders, calcitriol and related compounds has been advocated in chronicrenal failure to prevent multi-system toxicity caused by PTH. Potassiumdepletion and hypokalemia are common in cats with chronic renal failure.Oral supplementation of potassium in the form of potassium gluconate(Tumil K, RenaKare, Kolyum) or citrate is recommended. Holistic renaldrugs and compositions are also included in the present invention.Preferred holistic renal drugs include cranberry extract and mannose.Cranberry extract is purported to reduce the prevalence of urinary tractinfection which is a common risk factor for long-term decline of renalfunction. Renal drugs include typical small molecule pharmaceuticals,small proteins, macromolecular proteins and molecules, and antibodiesand further include vaccines designed to prevent renal disease.Antibodies include polyclonal and monoclonal antibodies andimmunoglobulin fragments such as Fv, Fab, Fab′, F(ab′)2, or otherantigen-binding antibody subsequences that interact with an antigen andperform the same biological function as a native antibody. The renaldrugs are administered to the patient using any method appropriate forthe renal drug and in amounts known to skilled artisans to be sufficientto treat or prevent renal disease.

In a further aspect, the present invention provides a method forpreventing or treating kidney disease. The method comprises feeding apatient a food composition comprising one or more food ingredientscontaining relatively low amounts of protein, sodium, and potassium. Themethod further comprises feeding a patient a food composition comprisingone or more food ingredients containing relatively low amounts ofprotein, sodium, and potassium in conjunction with a kidney diseasepreventing or treating amount of a renal drug.

In another aspect, the present invention provides a method forpreventing or treating kidney disease. The method comprises feeding apatient a food composition comprising one or more food ingredientscontaining relatively low amounts of protein. This aspect of theinvention is based upon the novel discovery that food compositionscontaining protein is certain amounts can prevent or treat kidneydisease while not causing the undesirable weight loss and muscle wastingcharacteristic of previously known food compositions having very lowamounts of protein. In various embodiments, the food composition usefulin the method comprises one or more food ingredients containing proteinin amounts of from about 5% to about 40%, preferably from about 8% toabout 25%, most preferably from about 10% to about 16%. The inventionalso provides a food composition for preventing or treating kidneydisease comprising one or more food ingredients containing relativelylow amounts of protein, preferably in amounts of from about 5% to about40%, more preferably from about 8% to about 25%, most preferably fromabout 10% to about 16%. In a further, embodiment, the method comprisesfeeding a patient a food composition comprising one or more foodingredients containing protein in amounts of from about 5% to about 30%,sodium in amounts of from about 0.01% to about 2%, potassium in amountsof from about 0.01% to about 2%, and phosphorous in amounts of fromabout 0.2% to about 1%.

In another aspect, the present invention provides a method formanufacturing a food composition suitable for preventing or treatingrenal disease. The method comprises admixing a food compositioncontaining extremely low amounts of one or more of protein, sodium, andpotassium and one or more supplements containing sufficient protein,sodium, or potassium to produce a food composition containing relativelylow amounts of protein, sodium, and potassium when the supplement(s) areadmixed with the food composition containing extremely low amounts ofone or more of protein, sodium, and potassium. In one embodiment, thefood composition comprises one or more food ingredients containingprotein in amounts of from about 5% to about 40%, sodium in amounts offrom about 0.01% to about 1%, and potassium in amounts of from about0.01% to about 1%.

In a further aspect, the present invention provides a kit comprising inseparate containers in a single package a food composition containingextremely low amounts of one or more of protein, sodium, and potassiumand one or more supplements containing sufficient protein, sodium, orpotassium to produce a food composition containing relatively lowamounts of protein, sodium, and potassium when the supplement(s) areadmixed with the food composition containing extremely low amounts ofone or more of protein, sodium, and potassium. The supplements can befood compositions containing protein, sodium, and\or potassium or can becompounds or other compositions suitable for consumption by a patient.Foods, minerals, and trace elements known to contain enriched amounts ofprotein, sodium, and potassium are particularly useful. Supplementsuseful for other diseases such as arthritis and supplements useful forcleaning teeth and ensuring fresh breath can be included, e.g., EPA,glucosamine, chondroitin sulfate, and SAMe. In other embodiments, thekit further comprises in separate containers in a single package or inseparate containers in a virtual package, as appropriate for the kitcomponent, at least one of (1) a renal drug, (2) a renal diagnosticdevice, (3) a means for communicating information about or instructionsfor admixing a food composition containing extremely low amounts of oneor more of protein, sodium, and potassium and one or more supplementscontaining sufficient protein, sodium, or potassium to produce a foodcomposition containing relatively low amounts of protein, sodium, andpotassium when the supplement(s) are admixed with the food compositioncontaining extremely low amounts of one or more of protein, sodium, andpotassium, (4) a means for communicating information about orinstructions for using a food composition comprising one or more foodingredients containing relatively low amounts of protein, sodium, andpotassium for preventing or treating kidney disease, (5) a means forcommunicating information about or instructions for administering inconjunction a food composition comprising one or more food ingredientscontaining relatively low amounts of protein, sodium, and potassium anda renal drug for preventing or treating kidney disease, and (6) a meansfor communicating information about or instructions for administering inconjunction a food composition comprising one or more food ingredientscontaining relatively low amounts of protein, sodium, and potassium andusing renal diagnostic devices for determining kidney function andevaluating the presence and severity of renal insufficiency ordysfunction. The kit components are typically in a separate package, inor on the package with one of the other kit components, or in a virtualpackage, as appropriate for the type of kit component. When the kitcomprises a virtual package, the kit is limited to the instructions in avirtual environment in combination with one or more of the otherphysical kit components.

In an additional aspect, the present invention provides a kit comprisingin separate containers in a single package or in separate containers ina virtual package, as appropriate, a food composition comprising one ormore food ingredients containing relatively low amounts of protein,sodium, and potassium and at least one of (1) a renal drug, (2) a renaldiagnostic device, (3) a means for communicating information about orinstructions for admixing a food composition containing extremely lowamounts of one or more of protein, sodium, and potassium and one or moresupplements containing sufficient protein, sodium, or potassium toproduce a food composition containing relatively low amounts of protein,sodium, and potassium when the supplement(s) are admixed with the foodcomposition containing extremely low amounts of one or more of protein,sodium, and potassium, (4) a means for communicating information aboutor instructions for using a food composition comprising one or more foodingredients containing relatively low amounts of protein, sodium, andpotassium for preventing or treating kidney disease, (5) a means forcommunicating information about or instructions for administering inconjunction a food composition comprising one or more food ingredientscontaining relatively low amounts of protein, sodium, and potassium anda renal drug for preventing or treating kidney disease, and (6) a meansfor communicating information about or instructions for administering inconjunction a food composition comprising one or more food ingredientscontaining relatively low amounts of protein, sodium, and potassium andusing renal diagnostic devices for determining kidney function andevaluating the presence and severity of renal insufficiency ordysfunction. The kit components are typically in a separate package, inor on the package with one of the other kit components, or in a virtualpackage, as appropriate for the type of kit component. When the kitcomprises a virtual package, the kit is limited to the instructions in avirtual environment in combination with one or more of the otherphysical kit components.

The food composition in a kit comprises one or more food ingredientscontaining relatively low amounts of protein, sodium, and potassium.

In some embodiments, the kits contain one or more renal diagnosticdevices for determining kidney function and evaluating the presence andseverity of renal insufficiency or dysfunction in a patient. The renaldiagnostic devices are typically in a separate package but may be in thepackage with one of the other kit components. The renal diagnosticdevices useful in the present invention include any device suitable fordetermining kidney function and evaluating the presence and severity ofrenal insufficiency or dysfunction in an animal. Preferred diagnosticmethods include serum urea nitrogen (SUN), creatinine levels, urinespecific gravity, and DNA damage, including urine assays for albuminsuch as those described in U.S. Pat. No. 6,589,748, U.S. Pat. No.6,447,989 and USPAN 20050026225 and comet trail assays. Diagnosticmethods are based upon known techniques including (1) blood markers suchas elevated blood urea nitrogen concentration, elevated serum creatinineconcentration, hyperphosphatemia, hyperkalemia or hypokalemia, metabolicacidosis and hypoalbuminemia, (2) urine markers such as impaired urineconcentrating ability, proteinuria, cylinduria, renal hematuria,inappropriate urine pH, inappropriate urine glucose concentration, andcystinuria, (3) physical, imaging, and diagnostic markers such as size,shape, location, and density, (4) single nucleotide polymorphisms (SNPs)such as those disclosed in WO 2004113570 A2, (5) genetic profiles thatare indicative of renal insufficiency or dysfunction, (6) proteomicprofiles that are indicative of renal insufficiency or dysfunction, and(7) metabolic profiles that are indicative of renal insufficiency ordysfunction. These diagnostic methods and devices (e.g., test strips,ELISA assays, comet assays,) based upon such methods are commonlyavailable to skilled artisans such as scientists and health careprofessionals and many are available to consumers, e.g., the HeskaCorporation's (Fort Collins Colo.) E.R.D.-HealthScreen Urine Tests thatdetects small amounts of albumin in the urine (“microalbuminuria”).

The kits provide a food composition comprising one or more foodingredients containing protein in amounts of from about 5% to about 40%,sodium in amounts of from about 0.01% to about 1%, and potassium inamounts of from about 0.01% to about 1%.

In another aspect, the present invention provides a means forcommunicating information about or instructions for (1) using a foodcomposition containing relatively low amounts of protein, sodium, andpotassium for preventing or treating kidney disease, (2) administeringin conjunction a food composition comprising one or more foodingredients containing relatively low amounts of protein, sodium, andpotassium and a renal drug for preventing or treating kidney disease,(3) admixing and administering a food composition containing extremelylow amounts of one or more of protein, sodium, and potassium and one ormore supplements containing sufficient protein, sodium, or potassium toproduce a food composition containing relatively low amounts of protein,sodium, and potassium when the supplement(s) are admixed with the foodcomposition containing extremely low amounts of one or more of protein,sodium, and potassium, (4) using a kit of the present invention forpreventing or treating renal disease, and (5) administering inconjunction a food composition comprising one or more food ingredientscontaining relatively low amounts of protein, sodium, and potassium andusing renal diagnostic devices for determining kidney function andevaluating the presence and severity of renal insufficiency ordysfunction. The communicating means comprises a document, digitalstorage media, optical storage media, audio presentation, or visualdisplay containing the information or instructions. Preferably, thecommunication is a displayed web site or a brochure, product label,package insert, advertisement, or visual display containing suchinformation or instructions. Useful information includes one or more of(1) methods and techniques for manufacturing and/or administering thefood compositions of the invention and renal drugs, (2) information forusing the renal diagnostic devices, (3) details about the side effects,if any, caused by using the present invention in combination with otherdrugs, and (4) contact information for patients to use if they have aquestion about the invention and its use. Useful instructions includedosages, administration amounts and frequency, and administrationroutes. The communication means is useful for instructing a patient onthe benefits of using the present invention and communicating theapproved methods for administering the invention to a patient.

The compositions, methods, and kits are useful for decreasing themorbidity and mortality for patients susceptible to or suffering fromkidney disease.

EXAMPLES

This invention can be further illustrated by the following examples ofpreferred embodiments thereof, although it will be understood that theseexamples are included merely for purposes of illustration and are notintended to limit the scope of the invention unless otherwisespecifically indicated.

Example 1 Canine Study

Study Design: This study utilized 10 healthy geriatric beagle dogs (10years old or over) per group (40 dogs total). The dogs were determinedto be healthy by physical exam and blood chemistry screen. Dogs withconfirmed renal failure, cancer, arthritis, hypothyroidism or otherdiseases were excluded. The dogs were cared for in accordance withInstitutional Animal Care and Use Committee protocols. The study designutilized a 30 day pre-feeding period followed by a 6 month test feedingperiod for a total of 7 months.

During the 30 day pre-feeding period, all dogs were fed a controlformula food. During the last week of the pre-feeding period, blood andurine samples were taken from each animal. Dual-energy x-rayabsorptiometry (DXA) scans pressure map analysis were also performed.The dogs were then blocked by age, gender and body fat percentage andassigned to 4 different treatment groups. Each group of dogs wasrandomly assigned to receive either the new Geriatric food or one ofthree competitor products.

During the 7 month test period, blood samples were drawn at 1 month, 3months and 6 months for analysis of biomarkers. Dogs were scanned by DXAat 3 months and 6 months to document changes in body composition andbone density. To assess changes in kidney health, urine microalbuminuriatests were performed at 3 months and 6 months. Throughout the durationof the study, body weights were recorded weekly and food intake recordeddaily. Additionally, dogs were offered enrichment toys, received routinegrooming and had daily opportunities for socialization with other dogsand people. Blood samples were also collected to determineproteomic/genomic marker differences over time.

Removal Criteria: If dogs were diagnosed with renal disease, cancer,hypothyroidism, Cushings or other disease, they were removed from thestudy and received treatment appropriate for their disease condition. Inaddition, dogs that refused to eat at least 25% of their assigned foodfor more than 4 days or had weight loss that exceeds 2.0%/weekly, theywere removed from the study. Other health issues or conditions thatarose during the study, such as diarrhea, were monitored and treated asneeded while attempting to maintain the dogs on the assigned treatmentfoods. If the necessary treatment involved switching dogs to anotherfood for more than 4 days, the dog was removed from the study.

Data was taken according to the Study Schedule shown below. The foodsused in the study are shown in Table 1. The data were collected usingthe Analytical Methods shown herein. The study was conducted using theFeeding and/or Treatment Administration regime shown below.

Study Schedule Study Day Procedure Measurement Sample Pre-Feeding PeriodDays 0-30 All dogs receive Control Food Intake daily Food Body Weight -weekly Day 30 Block by age, gender, 10 ml blood - body fat & assign toBiomarkers & groups & foods chemistry Screen 5 ml Urine - micro-albuminuria & specific gravity Test Feeding Period Days 31-210 Eachgroup of dogs Food intake - daily 10 ml blood - receive assigned foodBody weight - Biomarkers and weekly chemistry screen (day 61, 121, 211)5 ml Urine - micro- albuminuria and specific gravity (day 61, 121, 211)

TABLE 1 Analyzed Nutrient Profiles of the Four Foods Utilized in theStudy Nutrients, 100% Food Food Food Food Dry Matter Basis 61522 6229262794 62814 Crude Protein, % 20.10 27.65 27.76 29.39 Fat, % 16.45 13.5211.08 13.59 Ca, % 0.71 0.79 1.28 1.35 P, % 0.61 0.68 0.93 1.14 EPA, %0.32 0.10 <0.01 0.10 Total n-3 fatty 1.30 0.48 0.13 0.41 acids, % Totaln-6 fatty 3.96 3.10 1.79 2.66 acids, % Taurine, ppm 1400 1090 <100 1600Carnitine, ppm 314 55 19 84 Methionine, % 1.00 0.49 0.51 0.66 Cystine, %0.25 0.43 0.47 0.34 Manganese, ppm 87 77 71 69 Vitamin E, IU/kg 1492 594894 421 Vitamin C, ppm 127 288 86 21

Analytical Methods

Urine Samples: Microabluminuria were performed on all urine samplescollected during the study.

Blood Samples: Blood samples collected on days 0, 30 and 90 wereanalyzed for arthritic markers, antioxidant status markers, fatty acids,amino acids and chemistry screen to ensure the health of all animals onthe study.

Feeding and/or Treatment Administration Food 61526 Dry Food Dry FoodAmount per Amount per Weight Day Day (lbs) kcal/Day (cups) (cups)   0.537 ⅛ ⅛-⅛  1 62 ⅛ ⅛-¼   1.5 84 ¼ ¼-¼  2 104 ⅓ ¼-⅓   2.5 123 ⅓ ⅓-⅜  3 141⅜ ⅓-½  4 175 ½ ⅜-⅝  5 207 ⅝ ½-⅔  6 237 ⅔ ⅝-¾  7 266 ¾ ⅝-⅞  8 294 ⅞ ⅔-1 9 322 ⅞ ¾-1 10 348 1 ⅞-1⅛ 15 472 1⅓ 1⅛-1½ 20 585 1⅔ 1⅜-1⅞ 25 692 21⅝-2¼ 30 794 2¼ 1⅞-2⅝ 40 985 2¾ 2⅓-3¼ 50 1164 3¼ 2¾-3⅞ 60 1335 3¾ 3⅛-4⅜70 1498 4¼ 3½-4⅞ 80 1656 4⅔ 3⅞-5⅜ 90 1809 5⅛ 4⅓-5⅞ 100  1958 5½ 4⅝-6⅜Food 62794 Minimum Mid point Maximum, Weight, lbs Weight, kg food, gfood, g food, g  3-12 1.4-5.5 53 93 133 13-20 5.9-9.1 133 160 186 21-35 9.5-15.9 186 226 265 36-50 16.4-22.7 265 305 345 51-75 23.2-34.1 345398 451  76-100 34.5-45.5 451 504 557 Over 100 45.5+

Based on standard 8 oz cup (351 kcal/cup, 1510 kcal/lb, 3.3 kcal/gram,106 gram/cup)

Amounts are recommended for an average adult dog with normal activity.Food intake requirements vary depending on age, activity, andenvironment, and should be adjusted accordingly.

Food 62814 Minimum, Weight, lbs Weight, kg Grams/day 3 1.4 25 10 4.5 8020 9.1 115 30 13.6 150 40 18.2 185 50 22.7 215

These guideline amounts are a starting point and your dog may need morefood depending upon age, activity and temperament. To reach an optimalbody condition, you may need to adjust food intake. Feed this formula todogs up to 100 lbs, who are 7 years and older.

Food 62292 Weight, lbs Weight, kg Indoor Activity (1 hr) Activity (2 hr)26.4 12 165 185 205 30.8 14 185 205 230 35.2 16 200 230 255 39.6 18 220250 275 44.0 20 240 270 300 48.4 22 255 285 320 52.8 24 270 305 340 55.025 280 315 350

Optimal feeding amounts may vary with age, temperament and environment.

Example 2 Feline Study

Study Design: This study utilized 10 healthy geriatric cats (12 yearsold or over) per group (40 cats total). The cats were determined to behealthy by physical exam and blood chemistry screen. Cats with confirmedrenal failure, cancer, arthritis, hyperthyroidism or other diseases wereexcluded. The cats were located in the Hill's Pet Nutrition Center(Topeka, Kans.) and were cared for in accordance with InstitutionalAnimal Care and Use Committee protocols. The study design utilized a 30day pre-feeding period followed by a 6 month test feeding period for atotal test period of 7 months.

During the 30 day pre-feeding period, all cats were fed the controlformula food (Science Diet Senior without the antioxidant package).During the last week of the pre-feeding period, blood samples taken andDXA scans were performed. The cats were then blocked by age, gender andbody fat percentage and assigned to 3 different groups. Each group ofcats was randomly assigned to receive either the new geriatric food orone of three competitor products. All foods were formulated to meet orexceed AAFCO nutrient recommendations.

During the 7 month test period, blood samples were taken at 1 month, 3months and 6 months for analysis of biomarkers. Cats were scanned by DXAat 3 months and 6 months to document changes in body composition andbone density. To assess changes in kidney health, urine microalbuminuriatests were performed at 1 month, 3 months and 6 months. Throughout theduration of the study, body weight was recorded weekly and food intakerecorded daily. Additionally, cats were offered enrichment toys,received routine grooming and had daily opportunities for socializationwith other cats and people.

Removal Criteria: If at any point in the study, cats were diagnosed withrenal disease, cancer, hyperthyroidism, or other disease, they wereremoved from the study and received treatment appropriate for theirdisease condition. In addition, cats that refuse to eat at least 25% oftheir assigned food for more than 4 days or had weight loss that exceeds2.0%/week, were removed from the study. Other health issues orconditions that arose during the study, such as diarrhea, were monitoredand treated as needed while attempting to maintain the cats on theassigned treatment foods. If the necessary treatment involved switchingcats to another food for more than 4 days, the cat was removed from thestudy.

Data was taken according to the Study Schedule shown below. The foodsused in the study are shown in Table 2. The data were collected usingthe Analytical Methods shown herein. The study was conducted using theFeeding and/or Treatment Administration regime shown below.

The results of the study were analyzed to determine the affects ofvarious foods, food components, and nutrients on the kidney and theirusefulness for the prevention and/or treatment of kidney disease. Theresults show that relatively low levels of protein, sodium, andpotassium are beneficial for preventing and/or treating kidney disease.

Study Schedule Study Day Procedure Measurement Sample Pre-Feeding PeriodDays 0-30 All cats receive Food Intake daily Control Food Body weight -weekly Day 30 Block by age, gender, 10 ml blood - Biomarkers body fat &assign to & chemistry Screen groups & foods 5 ml Urine - micro-albuminuria & specific gravity Test Feeding Period Days 31-210 Eachgroup of dogs Food intake - daily 10 ml blood - Biomarkers receiveassigned food Body weight - and chemistry screen (day weekly 61, 121,211) 5 ml Urine - micro- albuminuria and specific gravity (day 61, 121,211)

TABLE 2 Analyzed Nutrient Profiles of the Four Foods Utilized in theStudy Key Nutrients, 100% Dry Matter Food Food Food Food Basis 6152662264 62695 62779 Crude Protein, % 35.73 34.85 30.52 40.45 Fat, % 22.4715.39 23.63 15.69 Ca, % 0.94 1.22 0.80 1.38 P, % 0.77 1.05 0.72 1.30DHA, % 0.23 0.08 0.11 0.07 EPA, % 0.32 0.07 0.13 0.07 Total n-3 fatty1.14 0.28 0.74 0.32 acids, % Total n-6 fatty 5.09 2.87 5.02 2.13 acids,% Taurine, ppm 2100 1800 1600 2100 Carnitine, ppm 367 28 90 28Methionine, % 1.32 1.05 0.72 0.77 Cystine, % 0.47 0.38 0.51 0.53Manganese, ppm 104 63 70 73 Vitamin E, IU/kg 1292 390 608 964 Vitamin C,ppm 141 12 511 110

Analytical Methods

Urine Samples: Microablumeria were performed on all urine samplescollected during the study.

Blood Samples: Blood samples collected on days 30, 59 and 120 and 210were analyzed for arthritic markers, antioxidant status markers, fattyacids, amino acids and chemistry screen to ensure the health of allanimals on the study.

Feeding and/or Treatment Administration Food 61526 Dry Food Dry FoodAmount per Amount per Weight Day Day (lbs) kcal/Day (cups) (cups)   0.528 ⅛ ⅛-⅛ 1 46 ⅛ ⅛-⅛   1.5 63 ⅛ ⅛-⅛ 2 78 ¼ ⅛-¼   2.5 92 ¼ ¼-¼ 3 106 ¼ ¼-⅓4 131 ⅓ ¼-⅜ 5 155 ⅜ ⅓-½ 6 178 ½ ⅜-½ 7 200 ½ ⅜-⅝ 8 221 ½ ½-⅝ 9 241 ⅝ ½-⅔10  261 ⅔ ½-¾ 15  354 ⅞ ¾-1 Food 62779 Minimum Maximum, Weight, lbsWeight, kg food, g Mid point food, g food, g 5-9 2-4 35 44 53 10-14 4-671 89 106

It is important that you feed Purina ONE to your adult cat “free choice”throughout the day, rather than as just a single feeding only atmealtime. Food intake required to maintain ideal body condition willvary, depending on age, activity, and environment. Watch your cat'sweight and adjust food amounts accordingly. If you have a kitten,pregnant or nursing cat you should continue feeding ONE Growth andDevelopment formula for kittens.

Food 62264 Minimum Maximum, Weight, lbs Weight, kg food, g Mid pointfood, g food, g 4 2 25 30 35 8 4 50 60 70 12 6 75 88 100 16 8 95 115 13522 10 120 145 170

The chart lists the approximate amount of food your cat will need dailyto maintain a healthy body weight (Portions are based on the use of astandard 8 ounce measuring cup). Your cat may eat more or less dependingon age, temperament and activity. Adjust to maintain ideal body weight.

Food 62695 Weight, lbs Weight, kg Lean Ideal Overweight 4-7 2-3 51 51 41 7-11 3-5 82 68 51 11-15 5-7 102 89 82 15-22  7-10 136 115 102

-   -   Standard 8 oz measuring cup=102 grams. Optimal feeding amounts        may vary according to your cat's temperament, activity level,        and environment.

Calculations and Statistics

Data from both Examples were analyzed using General Linear Modelsprocedure of SAS to determine treatment means. The experimental unit wasdog or cat and day 0 was used as a covariate. The geriatric food wasthen compared to the three other foods. Differences were consideredsignificant when P<0.05 and trends were determined when P<0.10.

Results

The results of the two studies were analyzed to determine the affects ofvarious foods, food components, and nutrients on the kidney and theirusefulness for the prevention and/or treatment of kidney disease. Theresults show that food compositions containing relatively low levels ofprotein, sodium, and potassium are beneficial for preventing and/ortreating kidney disease.

In the specification, there have been disclosed typical preferredembodiments of the invention and, although specific terms are employed,they are used in a generic and descriptive sense only and not forpurposes of limitation, the scope of the invention being set forth inthe following claims. Obviously many modifications and variations of thepresent invention are possible in light of the above teachings. It istherefore to be understood that within the scope of the appended claimsthe invention may be practiced otherwise than as specifically described.

1-7. (canceled)
 8. A method for preventing or treating kidney diseasecomprising feeding a patient a food composition comprising one or morefood ingredients containing relatively low amounts of protein, sodium,and potassium.
 9. The method of claim 8 wherein the food compositioncontains protein in amounts of from about 5% to about 40%, sodium inamounts of from about 0.01% to about 1%, and potassium in amounts offrom about 0.01% to about 1%.
 10. The method of claim 8 wherein the foodcomposition contains protein in amounts of from about 8% to about 25%,sodium in amounts of from about 0.05% to about 0.6%, and potassium inamounts of from about 0.05% to about 0.6%.
 11. The method of claim 8wherein the food composition contains protein in amounts of from about10% to about 20%, sodium in amounts of from about 0.1% to about 0.5%,and potassium in amounts of from about 0.1% to about 0.5%.
 12. Themethod of claim 8 wherein the food composition further comprisingphosphorous in amounts of from about 0.2% to about 1%.
 13. The method ofclaim 8 further comprising feeding the food composition in conjunctionwith a kidney disease preventing or treating amount of a renal drug. 14.The method of claim 8 wherein the patient is a canine or a feline. 15.The method of claim 8 wherein the food is a canned moist food or a dryfood. 16-24. (canceled)
 25. A method for preventing or treating kidneydisease comprising feeding a patient a food composition comprising oneor more food ingredients containing relatively low amounts of protein.26. The method of claim 25 wherein the food composition contains proteinin an amount of from about 5% to about 40%.
 27. The method of claim 25wherein the food composition contains protein in an amount of from about8% to about 25%.
 28. The method of claim 25 wherein the food compositioncontains protein in an amount of from about 10% to about 20%. 29-32.(canceled)